Study on Arctic Mining in Greenland

The Arctic region has a huge business potential and offers many possibilities, but to some extent, Arctic markets are not very familiar to most companies. It is therefore important to provide information about the markets, their characteristics and the operating context. This report gives an overview of the mining market and context in Greenland. Mining activities have so far been limited in Greenland considering the potential. A relatively weak record of mining activity appears to contrast with the metal endowment and existence of numerous mineral occurrences and several world class mineral deposits. Mineral exploration and mining in Greenland often occur in remote areas, usually far from existing infrastructure. This necessitates expensive transportation and establishment infrastructure. The remoteness, harsh Arctic climate and rugged terrain are negative factors often resulting in extra expenditures compared to most other jurisdictions. The many deep fjords in Greenland offer excellent opportunities for deep-sea port and shipping capacity. The social license to operate is in general very favourable in Greenland, and an ambitious new mineral strategy can be instrumental to attract new investments to mining in Greenland. Currently, Greenland is undergoing a phase of rapid development, and large government-funded infrastructure projects are in progress including new airports. Riikka Aaltonen, TEM, +358 295 064 216 Mikko Martikainen, TEM, +358 295 064 795 Pekka Tuomela, GTK, +358 50 300 563

The galactose elimination capacity and mortality in 781 Danish patients with newly-diagnosed liver cirrhosis: a cohort study

<p>Abstract</p> <p>Background</p> <p>Despite its biologic plausibility, the association between liver function and mortality of patients with chronic liver disease is not well supported by data. Therefore, we examined whether the galactose elimination capacity (GEC), a physiological measure of the total metabolic capacity of the liver, was associated with mortality in a large cohort of patients with newly-diagnosed cirrhosis.</p> <p>Methods</p> <p>By combining data from a GEC database with data from healthcare registries we identified cirrhosis patients with a GEC test at the time of cirrhosis diagnosis in 1992–2005. We divided the patients into 10 equal-sized groups according to GEC and calculated all-cause mortality as well as cirrhosis-related and not cirrhosis-related mortality for each group. Cox regression was used to adjust the association between GEC and all-cause mortality for confounding by age, gender and comorbidity, measured by the Charlson comorbidity index.</p> <p>Results</p> <p>We included 781 patients, and 454 (58%) of them died during 2,617 years of follow-up. Among the 75% of patients with a decreased GEC (<1.75 mmol/min), GEC was a strong predictor of 30-day, 1-year, and 5-year mortality, and this could not be explained by confounding (crude hazard ratio for a 0.5 mmol/min GEC increase = 0.74, 95% CI 0.59–0.92; adjusted hazard ratio = 0.64, 95% CI 0.51–0.81). Further analyses showed that the association between GEC and mortality was identical for patients with alcoholic or non-alcoholic cirrhosis etiology, that it also existed among patients with comorbidity, and that GEC was only a predictor of cirrhosis-related mortality. Among the 25% of patients with a GEC in the normal range (≥ 1.75 mmol/min), GEC was only weakly associated with mortality (crude hazard ratio = 0.79, 95% CI 0.59–1.05; adjusted hazard ratio = 0.80, 95% CI 0.60–1.08).</p> <p>Conclusion</p> <p>Among patients with newly-diagnosed cirrhosis and a decreased GEC, the GEC was a strong predictor of short- and long-term all-cause and cirrhosis-related mortality. These findings support the expectation that loss of liver function increases mortality.</p

Human 13N-ammonia PET studies: the importance of measuring 13N-ammonia metabolites in blood

Dynamic 13N-ammonia PET is used to assess ammonia metabolism in brain, liver and muscle based on kinetic modeling of metabolic pathways, using arterial blood 13N-ammonia as input function. Rosenspire et al. (1990) introduced a solid phase extraction procedure for fractionation of 13N-content in blood into 13N-ammonia, 13N-urea, 13N-glutamine and 13N-glutamate. Due to a radioactive half-life for 13N of 10 min, the procedure is not suitable for blood samples taken beyond 5–7 min after tracer injection. By modifying Rosenspire’s method, we established a method enabling analysis of up to 10 blood samples in the course of 30 min. The modified procedure was validated by HPLC and by 30-min reproducibility studies in humans examined by duplicate 13N-ammonia injections with a 60-min interval. Blood data from a 13N-ammonia brain PET study (from Keiding et al. 2006) showed: (1) time courses of 13N-ammonia fractions could be described adequately by double exponential functions; (2) metabolic conversion of 13N-ammonia to 13N-metabolites were in the order: healthy subjects > cirrhotic patients without HE > cirrhotic patients with HE; (3) kinetics of initial tracer distribution in tissue can be assessed by using total 13N-concentration in blood as input function, whereas assessment of metabolic processes requires 13N-ammonia measurements

European regulatory agenices should employ full time statisticians

No abstract available

Prevalent cases in observational studies of cancer survival: do they bias hazard ratio estimates?

Observational epidemiological studies often include prevalent cases recruited at various times past diagnosis. This left truncation can be dealt with in non-parametric (Kaplan–Meier) and semi-parametric (Cox) time-to-event analyses, theoretically generating an unbiased hazard ratio (HR) when the proportional hazards (PH) assumption holds. However, concern remains that inclusion of prevalent cases in survival analysis results inevitably in HR bias. We used data on three well-established breast cancer prognosticators – clinical stage, histopathological grade and oestrogen receptor (ER) status – from the SEARCH study, a population-based study including 4470 invasive breast cancer cases (incident and prevalent), to evaluate empirically the effectiveness of allowing for left truncation in limiting HR bias. We found that HRs of prognostic factors changed over time and used extended Cox models incorporating time-dependent covariates. When comparing Cox models restricted to subjects ascertained within six months of diagnosis (incident cases) to models based on the full data set allowing for left truncation, we found no difference in parameter estimates (P=0.90, 0.32 and 0.95, for stage, grade and ER status respectively). Our results show that use of prevalent cases in an observational epidemiological study of breast cancer does not bias the HR in a left truncation Cox survival analysis, provided the PH assumption holds true

N-(4-[18F]fluorobenzyl)cholylglycine, a novel tracer for PET of enterohepatic circulation of bile acids: radiosynthesis and proof-of-concept studies in rats

Enterohepatic circulation (EHC) of conjugated bile acids is an important physiological process crucial for regulation of intracellular concentrations of bile acids and their function as detergents and signal carriers. Only few bile acid-derived imaging agents have been synthesized and hitherto none have been evaluated for studies of EHC. We hypothesized that N-(4-[F]fluorobenzyl)cholylglycine ([F]FBCGly), a novel fluorine-18 labeled derivative of endogenous cholylglycine, would be a suitable tracer for PET of the EHC of conjugated bile acids, and we report here a radiosynthesis of [F]FBCGly and a proof-of-concept study by PET/MR in rats.A radiosynthesis of [F]FBCGly was developed based on reductive alkylation of glycine with 4-[F]fluorobenzaldehyde followed by coupling to cholic acid. [F]FBCGly was investigated in vivo by dynamic PET/MR in anesthetized rats; untreated or treated with cholyltaurine or rifampicin. Possible in vivo metabolites of [F]FBCGly were investigated by analysis of blood and bile samples, and the stability of [F]FBCGly towards enzymatic de-conjugation by Cholylglycine Hydrolase was tested in vitro.[F]FBCGly was produced with a radiochemical purity of 96% ± 1% and a non-decay corrected radiochemical yield of 1.0% ± 0.3% (mean ± SD; n = 12). PET/MR studies showed that i.v.-administrated [F]FBCGly underwent EHC within 40-60 min with a rapid transhepatic transport from blood to bile. In untreated rats, the radioactivity concentration of [F]FBCGly was approximately 15 times higher in bile than in liver tissue. Cholyltaurine and rifampicin inhibited the biliary secretion of [F]FBCGly. No fluorine-18 metabolites of [F]FBCGly were observed.We have developed a radiosynthesis of a novel fluorine-18 labeled bile acid derivative, [F]FBCGly, and shown by PET/MR that [F]FBCGly undergoes continuous EHC in rats without metabolizing. This novel tracer may prove useful in PET studies on the effect of drugs or diseases on the EHC of conjugated bile acids

Impairment of the Organization of Locomotor and Exploratory Behaviors in Bile Duct-Ligated Rats

Hepatic encephalopathy (HE) arises from acute or chronic liver diseases and leads to several problems, including motor impairment. Animal models of chronic liver disease have extensively investigated the mechanisms of this disease. Impairment of locomotor activity has been described in different rat models. However, these studies are controversial and the majority has primarily analyzed activity parameters. Therefore, the aim of the present study was to evaluate locomotor and exploratory behavior in bile duct-ligated (BDL) rats to explore the spatial and temporal structure of behavior. Adult female Wistar rats underwent common bile duct ligation (BDL rats) or the manipulation of common bile duct without ligation (control rats). Six weeks after surgery, control and BDL rats underwent open-field, plus-maze and foot-fault behavioral tasks. The BDL rats developed chronic liver failure and exhibited a decrease in total distance traveled, increased total immobility time, smaller number of rearings, longer periods in the home base area and decreased percentage of time in the center zone of the arena, when compared to the control rats. Moreover, the performance of the BDL rats was not different from the control rats for the elevated plus-maze and foot-fault tasks. Therefore, the BDL rats demonstrated disturbed spontaneous locomotor and exploratory activities as a consequence of altered spatio-temporal organization of behavior

Improved quantification of CO2 storage containment risks - an overview of the SHARP Storage project

Carbon Capture and Storage (CCS) is now maturing in Europe and worldwide with several Net Zero projects emerging. Hence, the need for safe and reliable CO2 storage sites is accelerating and the accurate assessment of large-scale storage options at the gigatonne-per-year is critical. The SHARP project addresses the main priority areas required to improve current technologies to deliver CO2 storage volumes at the scale needed to meet demands for large scale storage. Research needs identified in the industry has provided the base for this well-integrated project with the ambitions to reduce the uncertainty in the geomechanical response to CO2 injection. Six case studies from sites in the North Sea and India will be matured during the projects. Ongoing work includes review of existing stress data, updating and integration of seismic catalogues and planning of new experimental data for improved constitutive models and rock failure attributes. Improved data analysis, compiling data from different sources, and new data generated in the project is expected to provide a base for updated failure risk assessment and more targeted monitoring. An initial assessment of rock failure risk in in progress and will be updated with a "Round 2" failure assessment incorporating new learnings and more mature data. The improved failure risk assessment includes the use of Bayesian statistical approach for quantification of uncertainties in geomechanical properties. Methods to quantify geological containment risk will be developed by reading across event tree techniques from other industries (e.g. nuclear). A set of generic release diagrams have been derived in a series of interdisciplinary workshops as a starting point for risk modellingImproved quantification of CO2 storage containment risks - an overview of the SHARP Storage projectpublishedVersio

Sea-level rise in Denmark: paleo context, recent projections and policy implications

We present the most recent Intergovernmental Panel on Climate Change Sixth Assessment Report (AR6) sea-level projections for four Danish cities (Aarhus, Copenhagen, Esbjerg and Hirtshals) under the Shared Socioeconomic Pathway (SSP) family of climate scenarios. These sea-level changes projected over the next century are up to an order of magnitude larger than those observed over the previous century. At these cities, year 2150 sea-level changes of between 29 and 55 cm are projected under the very low emissions scenario (SSP1-1.9), while changes of between 99 and 123 cm are projected under the very high emissions scenario (SSP5-8.5). These differences highlight the potentially significant impact of remaining opportunities for climate change mitigation. Due to this increase in mean sea level, the mean recurrence time between historically extreme events is expected to decrease. Under the very high emissions scenario, the historical 100-year storm flood event will become a 1- to 5-year event at most Danish harbours by 2100. There is considerable uncertainty associated with these sea-level projections, primarily driven by uncertainty in the future evolution of the Antarctic ice sheet and future sterodynamic changes in ocean volume. The AR6 characterises collapse of the West Antarctic ice sheet as a low-probability but high-impact event that could cause several metres of sea-level rise around Denmark by 2150. In climate adaptation policy, the scientific landscape is shifting fast. There has been a tremendous proliferation of diverse sea-level projections in recent years, with the most relevant planning target for Denmark increasing c. 50 cm in the past two decades. Translating sea-level rise projections into planning targets requires value judgments about acceptable sea-level risk that depend on local geography, planning timeline and climate pathway. This highlights the need for an overarching national sea-level adaptation plan to ensure municipal plans conform to risk and action standards